Aberrant production of ceramides, the precursors of complex sphingolipids, is a hallmark of obesity and strongly linked to metabolic dysfunction (Meikle and Summers 2017). Ceramides are formed by recycling or de novo synthesis from sphingosine and a fatty acid side chain moiety. The side chain length determines lipotoxicity of ceramides, as those composed of C16:0 or C18:0 side chains are toxic whereas those with C24:0 or C24:1 are not (Meikle and Summers 2017). Counteracting the deleterious effects of high-fat diets (HFDs) rich in saturated fat either by inhibiting synthesis or by promoting degradation of ceramides mitigates insulin resistance and ectopic lipid accumulation (Meikle and Summers 2017). However, drugs that safely and selectively target ceramide metabolism have failed to translate into metabolic benefit in human trials so far.

中文翻译：

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融合线粒体，失去食欲：一种抗厌食、抗肥胖的鞘脂

神经酰胺（复杂鞘脂的前体）的异常产生是肥胖的标志，并且与代谢功能障碍密切相关（Meikle 和 Summers 2017）。神经酰胺是通过鞘氨醇和脂肪酸侧链部分的回收或从头合成而形成的。侧链长度决定神经酰胺的脂毒性，因为那些由 C16:0 或 C18:0 侧链组成的神经酰胺是有毒的，而那些由 C24:0 或 C24:1 组成的则没有毒性（Meikle 和 Summers 2017）。通过抑制神经酰胺的合成或促进神经酰胺的降解来抵消富含饱和脂肪的高脂饮食 (HFD) 的有害影响，可以减轻胰岛素抵抗和异位脂质积累 (Meikle 和 Summers 2017)。然而，迄今为止，安全且选择性地靶向神经酰胺代谢的药物尚未在人体试验中转化为代谢益处。